Week 5 Flashcards
What kind of response does adrenergic stimulation cause?
Can be excitatory or inhibitory. Epinephrine and norepinephrine causes organs such as the heart, dilatory muscles of iris, and smooth muscles of blood vessels to contract (excite) and causes smooth muscles and other blood vessels to dilate (inhibit). Response is determined by receptor proteins, particularly alpha or beta adrenergic receptors
*What do each of the adrenergic receptors do
alpha 1 : Vasoconstriction in viscera and skin - contraction of smooth muscles
beta 1: Increased heart rate and contractility
beta 2: Dilation (relaxation) of bronchioles (lung) and blood vessels
How do adrenergic receptors act to cause cell response?
All act through G-proteins! Epinephrine/norepinephrine binding causes dissociation of alpha and beta/gamma. Depending on the case, either the alpha or beta/gamma interacts to open/close an ion channel or activate an enzyme.
Beta receptors produce effects through producing cAMP
Alpha receptors produce effects through a rise in cytoplasmic Ca2+ concentration
How does the alpha 2 adrenergic receptor work? What drug acts on these receptors?
Alpha 2 is located on the presynaptic boutons where it produces a decreased release of norepinephrine when activated by norepinephrine in the cleft. This is a negative feedback control over the amount of norepinephrine released.
The most medically important alpha 2 receptors are in the brain. They are stimulated by clonidine and produce a lowering of blood pressure by reducing activation of the entire sympathoadrenal system!
Summarize the fight or flight response
Norepinephrine released by postganglionic sympathetic axons and epinephrine released by adrenal medulla (into blood) boost the ability of the cardiovascular system to respond to physical emergencies.
Alpha adrenergic receptors (sensitive to norepinephrine) stimulate vasoconstriction
Beta adrenergic receptors (sensitive to epinephrine) stimulate increased heart rate and contractility. Also promote vasodilation in appropriate organs to prepare body for physical exertion.
Which neurons are cholinergic (release acetylcholine)? what types of responses do they cause and through which type of receptors?
All somatic motor neurons: always excitatory via nicotinic receptors in skeletal muscles and CNS
All preganglionic (sympathetic and parasympathetic): always excitatory via nicotinic receptors in autonomic ganglia
Most postganglionic parasympathetic: usually excitatory but can be inhibitory via muscarinic receptors in visceral organs
drugs that block ACh receptors
Curare (tubocurarine) blocks nicotinic ACh receptors
Atropine (belladonna) blocks muscarinic ACh receptors
review how the two types of ACh receptors work
Nicotinic: ligand gated ion channel opens when ACh binds and allows Na+ and K+ to flow in/out. Na+ movement is the dominant effect and causes depolarization and excitation.
Muscarinic: coupled to G-proteins which can open or close different membrane channels and activate different enzymes producing either excitation of inhibition.
Most visceral organs receive what type of innervation from sympathetic and parasympathetic systems?
Dual innervation: innervated by both sympathetic and parasympathetic fibers in either antagonistic, complementary, or cooperative ways.
Give 2 examples of antagonistic effects of sympathetic and parasympathetic systems
In the pacemaker region of the heart, adrenergic stimulation from the sympathetic fibers increases heart rate while ACh release from parasympathetic fibers decreases heart rate. The heart rate can therefore be increased by two ways:
- Parasympathetic activity decreases - major determinant, occurs early in exercise
- Sympathetic activity increases - during intense exercise
A reverse of this example is seen in the digestive tract where sympathetic nerves inhibit and parasympathetic nerves stimulate (pretty much the only exception to sympathetic=speed up and para= slow down)
Explain the effects of the sympathetic and parasympathetic systems on the diameter of the pupil of the eye
Sympathetic nerves cause dilation by contraction of the radial muscles
Parasympathetic nerves cause constriction by contraction of the circular muscles
Explain the general features of endocrine glands and which organs are endocrine glands
Endocrine glands lack ducts while exocrine glands have ducts (secrete sweat). Endocrine glands secrete hormones into the blood to interact with target cells containing the specific receptor for the hormone. Many endocrine glands are organs whose primary function is production and secretion of hormones. However, many other organs secrete hormones and so are also considered endocrine glands (like heart, adipose, kidneys)
Sometimes chemical messengers (neurotransmitters) are secreted into blood, especially from the hypothalamus. These are called neurohormones and include norepinephrine, for example.
compare neurotransmitters and hormones
Both involve changes in ion flow and membrane potential. Both must interact with a specific receptor protein to cause a specific sequence of changes and there must be a mechanism to turn off the action (rapid removal or chemical inactivation)
The only main difference is that neurotransmitters do not travel in the blood but instead diffuse across a narrow synaptic cleft.
In fact, the same molecule can serve as both a neurotransmitter AND a hormone!
Give a brief overview of the classifications of hormones
Amines: derived from amino acids tyrosine and tryptophan. Secreted by adrenal medulla, thyroid, and pineal glands
Polypeptides and proteins: distinction is blurry, proteins are just large peptides (over 100 amino acids). ADH is polypeptide (small) while Insulin is messier (2 short peptides joined)
Glycoproteins: consist of protein bound to one or more carbohydrate groups. Includes FSH and LH
Steroids: derived from cholesterol. Includes testosterone, estradiol, progesterone, cortisol. Secreted by adrenal cortex and gonads only
Which hormones are lipophilic/non polar/water insoluble? Where are they made?
Steroid hormones: secreted by only 2 glands, the adrenal cortex and the gonads. Gonads secrete sex steroids while adrenal cortex secretes corticosteroids.
Thyroid hormones: composed of two tyrosines bonded together, if it has 4 iodine molecules it is called tetraiodothyronine, T4, or thyroxine. If it has 3 iodine molecules it is triiodothyronine or T3.
Which hormones are polar/water soluble?
Polypeptides
Proteins
Glycoproteins
Catecholamines (derived from amino acid tyrosine and so are similar to polypeptides)
Explain how polarity of a hormone affects its ability to be deliverable as a drug
Nonpolar hormones can be taken as oral pills because they can pass through the cell membrane. Birth control pills (steroid hormones) and thyroid hormone pills (for hypothyroid treatment) are oral drugs.
Polar hormones cannot be taken orally because they would be digested before being absorbed in the blood. Polypeptides and glycoproteins must be injected
Can melatonin be taken orally?
Melatonin, derived from amino acid tryptophan, can pass through plasma membranes despite its similarities to the polar hormones. It can be take orally
Features of receptor proteins
Specificity
Affinity (high bond strength)
Low capacity - there’s a limited number of receptors per target cell so saturation is possible
How are lipophilic and water soluble hormones transported to target cells?
water soluble are transported in the blood because they can dissolve in the aqueous portion.
lipophilic cannot dissolve in blood so are transported by plasma carrier proteins which they dissociate from to enter the plasma membrane.
What type of proteins are lipophilic hormone receptors? what do they cause in the cell?
They are Nuclear Hormone Receptors because they are within the cell nucleus where they activate genetic transcription by functioning as Transcription Factors. The altered mRNA production directs protein synthesis and changes metabolism of the target cell.
This is called Genomic Action:
steroid hormone enters cell and binds receptor in cytoplasm. It translocates to the nucleus and binds to Hormone Response Elements in the DNA, stimulating transcription
What is tamoxifen and what does it tell us about the effects of hormones
a Selective Estrogen Receptor Modulator (SERM) which acts like estrogen in one organ while antagonizing estrogen in another. Demonstrates that organ response to a hormone is variable based on regulatory proteins called coactivators and corepressors which regulate transcription factors
*Explain the major hormone secreted by the thyroid gland vs the active thyroid hormone
Major hormone is Thyroxine or Tetraiodothyronine (T4). Thyroxine travels in blood attached to carrier proteins called thyroxine-binding globulin (TBG). There is only a small amount of Triiodothyronine (T3) made by the thyroid. Carrier proteins have a high affinity for T4 so unbound T3 is very high. Only free thyroxine and T3 can enter target cells (the carrier bound molecules serve as a reservoir). Once free T4 passes into the cell, it is converted to T3. So, it is T3, not T4, which is the active thyroid hormone in target cells! T3 uses non-specific stepping stone proteins to enter the nucleus and bind its receptor, which is always in the nucleus.
*Why does it take a few weeks for symptoms of hypothyroidism to set in?
There is a reservoir of thyroxine (T4, tetraiodothyronine) contained in the blood on thyroxine-binding globulin carriers. The reservoir allows thyroid hormone to still exert its effect for a while after the thyroid is removed.